Drug-carriers and associated delivery methods are needed for certain drugs, which are only effective if delivered in a targeted fashion to a specific receptor site. Nanocarrier drug delivery systems, such as organic nanoparticles, offer several advantages when compared to conventional methods for delivering such drugs. Some of these potential advantages include an increased blood circulation time (Litzinger D C, et al., “Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes,” 1994, Biochim Biophys Acta, Biomembr 1190:99-107), an enhanced ability to permeate cellular membranes, and an increased retention time at the targeted receptor site (Allen T M, et al., “Drug Delivery Systems: Entering the Mainstream,” 2004, Science 303:1818-1822; Duncan R, et al., “Drug targeting in cancer therapy: the magic bullet, what next?” J Drug Targeting, 1996, 3:317-319). Because the aforementioned advantages are dependent on the nanocarrier's physical dimensions and properties, it is important to control the size of the nanocarrier, often below 100 nm in diameter, as well as the nanocarrier's surface properties.
Flash nanoprecipitation (FNP) is a technique that has been used to produce organic nanoparticles containing drugs with a Log P greater than about 6, based on the anti-solvent precipitation principle and the use of amphiphilic diblock copolymers. FNP has been used to produce suspensions of these organic nanoparticles having an average diameter below 200 nm and containing hydrophobic compounds or drugs such as β-carotene (Log P=15.5); paclitaxel (Log P=7.38); and bifenthrin (Log P=6.0) (Zhu, Z., et al., “Formation of Block Copolymer-Protected Nanoparticles via Reactive Impingement Mixing”, 2007, Langmuir, 23:10499-10504; also Saad, W. S., “Drug nanoparticle formation via flash nanoprecipitation: Conjugation to encapsulate and control the release of paclitaxel,” Ph.D. Dissertation, Princeton University, 2007; also Liu, Y. et al., “Stabilized polymeric nanoparticles for controlled and efficient release of bifenthrin,” 2008, Pest Manage Sci, 64:808-812). However, FNP has not been used to produce stable organic nanoparticles containing drugs that have a Log P less than about 6. Nanoparticles produced by FNP with drugs having a Log P lower than 6 were shown to be unstable towards aggregation and particle growth, i.e., Oswald ripening.
Accordingly, there is a need in the field, to which the present invention pertains, for stable organic nanoparticles that contain drugs having a Log P less than 6. Surprisingly, the present invention fulfills this as well as other related needs in the field.